Our objective is to analyze the mechanism(s) active in the immunoregulation of the developing and involuting granulomas in Schistosoma mansoni infected mice. To this end, we started to delineate the subpopulations of lymphocytes active in the generation and suppression of the granulomatous response. In vitro, analysis of migration inhibition factor (MIF) production revealed, that mediator producing splenic lymphocytes belong to the T lineage and the Lytl ion subset. In contrast splenic T lymphocytes which suppressed mediator production belong to the LYt2 ion subsets bearing I-J and I-C subregion determinants. Thus, modulation of mediator production in vitro may reflect a similar mechanism active in vivo in the diminished granulomatous response. Macrophages, especially those which compose the granulomas may also participate in the regulation of the inflammatory response. Delineation of Fc and C3 receptors as well as the display of Ia antigens on the macrophage membranes revealed differences between cells originating from vigorous as opposed to those isolated from modulated liver lesions. Differences in the density of Fc receptors were also reflected in the phagocytic capacity of the cells. Macrophages of the liver and lung granulomas seemed to be the source of angiotension converting enzyme activity. Increased enzyme levels were found in the involuting lesions. Further studies are conducted in analyzing the lymphocyte and macrophage populations of the granuloma.